Cervical cancer screening is shifting from Pap cytology to primary HPV testing. While HPV testing provides greater reassurance for HPV-negative women, additional tests are needed for HPV-positive women to decide who needs further diagnostic evaluation or treatment. We have developed a novel HPV triage strategy based on automated evaluation of cervical cytology slides stained with p16 and Ki-67 (dual stain). In the initial evaluation, this approach has shown improved accuracy compared to Pap testing and manual dual stain. Now, we are evaluating the approach in a large population of HPV-positive women enrolled in the IRIS cohort.